The relevance of primary tumour location in patients with metastatic colorectal cancer: A meta-analysis of first-line clinical trials

被引:426
作者
Holch, Julian Walter [1 ,2 ]
Ricard, Ingrid [3 ]
Stintzing, Sebastian [1 ,2 ]
Modest, Dominik Paul [1 ,2 ]
Heinemann, Volker [1 ,2 ]
机构
[1] Ludwig Maximilians Univ Munchen, Univ Hosp Grosshadern, Dept Med Oncol, Marchioninistr 15, D-81377 Munich, Germany
[2] Ludwig Maximilians Univ Munchen, Univ Hosp Grosshadern, Ctr Comprehens Canc, Marchioninistr 15, D-81377 Munich, Germany
[3] Ludwig Maximilians Univ Munchen, Inst Med Informat Biometry & Epidemiol, Marchioninistr 15, D-81377 Munich, Germany
关键词
Metastatic colorectal cancer; Primary tumour location; Sidedness; Prognostic biomarker; Predictive biomarker; Cetuximab; Panitumumab; Bevacizumab; Anti-EGFR; Anti-VEGF; COLON-CANCER; 2; SIDES; CETUXIMAB; DISTAL; EXPRESSION; PREDICTOR; BENEFIT; STAGE; SITE;
D O I
10.1016/j.ejca.2016.10.007
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Retrospective subgroup analyses suggest that primary tumour location (PTL) has a prognostic importance and relates to response to targeted therapy. Methods: We conducted a meta-analysis of first-line clinical trials available up to October 2016, which assessed the relevance of PTL in patients with metastatic colorectal cancer (mCRC). Right- and left-sided colorectal cancers were differentiated (RC and LC). Results: In 13 first-line randomised controlled trials and one prospective pharmacogenetic study, RC was associated with a significantly worse prognosis compared with LC (hazard ratio [HR] for overall survival: 1.56; 95% confidence interval [CI]: 1.43-1.70; P < 0.0001). A meta-analysis of PRIME and CRYSTAL study suggests that PTL was predictive of survival benefit from addition of anti-EGFR antibody to standard chemotherapy in patients with RAS wildtype tumour (overall survival, HR for LC: 0.69; 95% CI: 0.58-0.83; P < 0.0001 and HR for RC: 0.96; 95% CI: 0.68-1.35; P = 0.802). A meta-analysis of FIRE-3/AIO KRK0306, CALGB/SWOG 80405 and PEAK study indicates that patients with RAS wild-type LC had a significantly greater survival benefit from anti-EGFR treatment compared with anti-VEGF treatment when added to standard chemotherapy (HR 0.71; 95% CI: 0.58-0.85; P = 0.0003). By contrast, in patients with RC, benefit from standard therapy was poor and bevacizumab-based treatment was numerically associated with longer survival (HR 1.3; 95% CI: 0.97-1.74; P = 0.081). Conclusions: The present meta-analysis demonstrates that PTL is prognostic in mCRC. Further, it supports the conclusion that patients with left-sided RAS wild-type mCRC should be preferentially treated with an anti-EGFR antibody. In right-sided mCRC, chemotherapy plus bevacizumab is a treatment option, but optimal treatment has yet to be defined. (C) 2016 Elsevier Ltd. All rights reserved.
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收藏
页码:87 / 98
页数:12
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